The glutamate receptor agonist NMDA can markedly stimulate LH secretion in female rhesus macaques, especially during the luteal phase of the menstrual cycle. In this study, a potent gonadotropin-releasing hormone (GnRH) antagonist (D-Phe2, Pro3, D-Phe6]-LHRH) was administered (0.4 mg/kg BW, i.v.) to luteal-phase macaques, 20 min before administration of NMDA (10 mg/kg BW, i.v.), and was found to significantly attenuate the NMDA-induced increase in plasma LH concentrations. Attenuation of the NMDA-induced LH response was also achieved through the administration of MK-801, a non-competitive NMDA receptor antagonist (2 mg/kg BW, i.v.). However, MK-801 had no suppressive effect on the tonic plasma LH levels of cycling intact macaques nor on the high-amplitude pulsatile LH release pattern of ovariectomized macaques; if anything, it paradoxically resulted in an acute stimulation. Furthermore, the administration of NMDA (10 mg/kg BW, i.v.) to ovariectomized macaques caused an acute inhibition of pulsatile LH secretion, whereas an acute stimulation might have been expected based on the neuroexcitatory properties of NMDA. Taken together, these data demonstrate that in rhesus macaques excitatory amino acids can markedly increase plasma LH concentrations, and that this action is most likely mediated through enhanced GnRH secretion. On the other hand, because the MK-801-induced blockade of NMDA receptors failed to suppress LH secretion, it is questionable whether endogenous glutamate, acting through NMDA receptors, plays a major physiological role in modulating the pulsatile pattern of LH secretion in higher primates. (Findings from this study were presented in 1996 at the International Congress of Endocrinology, held in San Francisco, CA).